Interaction between basic fibroblast growth factor and the anti-angiogenic drug PNU145156E

Moreno Zamai, Chithra Hariharan, Dina Pines, Michal Safran, Avner Yayon, Valeria R. Caiolfa, Mariangela Mariani, Ehud Pines, Rivka Cohen-Luria, Abraham H. Parola

Research output: Contribution to journalArticlepeer-review

Abstract

Solid tumors require the formation of a vascular network derived from host blood vessels to support their growth. The heparin-binding growth factor family was the first class of angiogenesis factors to be studied. These proteins play key roles in a variety of crucial biological activities that require cell growth, differentiation, migration and chemotaxis. Our work presents the study of a group of polyanionic compounds, the naphthalene sulfonic distamycin A derivatives, named suradistas, which represents a new class of inhibitors of neo-angiogenesis that can counteract vascularization of solid tumors. By a combination of in vitro and in vivo approaches, a leader compound, PNU145156E, was selected. The results suggest that PNU145156E interacts directly with the heparin-binding growth factor bFGF in a specific manner. It forms a tight but reversible 1 to 1 complex with the protein, inducing conformational changes, which render bFGF less stable, preventing the interaction with heparin and the biologically effective dimerization of the growth factor.

Original languageEnglish
Pages (from-to)23-35
Number of pages13
JournalJournal of Molecular Structure
Volume792-793
DOIs
Publication statusPublished - Jul 3 2006

Keywords

  • Angiogenesis
  • bFGF
  • Cancer
  • Fluorescence spectroscopy
  • Heparin-binding growth factors
  • Naphthalene sulfonic distamycin A derivatives
  • Suradista

ASJC Scopus subject areas

  • Structural Biology
  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Spectroscopy
  • Atomic and Molecular Physics, and Optics
  • Materials Science (miscellaneous)

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